Nature Medicine
11, 998 - 1004 (2005)
Published online: 14 August 2005; | doi:10.1038/nm1285
A genetic Xenopus laevis tadpole model to study lymphangiogenesisAnnelii Ny1, 5, Marta Koch1, 5, Martin Schneider1, 5, Elke Neven1, 5, Ricky T Tong2, 5, Sunit Maity1, Christian Fischer1, Stephane Plaisance1, Diether Lambrechts1, Christophe Héligon3, Sven Terclavers1, Malgorzata Ciesiolka1, Roland Kälin3, Wing Yan Man1, Irena Senn3, Sabine Wyns1, Florea Lupu4, André Brändli3, Kris Vleminckx1, Désiré Collen1, Mieke Dewerchin1, Edward M Conway1, Lieve Moons1, Rakesh K Jain2
& Peter Carmeliet11
Flanders Interuniversity Institute for Biotechnology, Center for Transgene Technology and Gene Therapy, Campus Gasthuisberg O&N, Herestraat 49, KULeuven, Leuven, B-3000 and Department of Molecular Biomedical Research, University of Ghent, Technology Park 927, Ghent, B-9052, Belgium. 2
Harvard Medical School, Edwin L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts
02114, USA. 3
Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, Wolfgang-Pauli Strasse 10, HCI, CH-8057
Zurich, Switzerland. 4
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, Oklahoma
73104, USA. 5
These authors contributed equally to this work.
Correspondence should be addressed to Peter Carmeliet peter.carmeliet@med.kuleuven.be Lymph vessels control fluid homeostasis, immunity and metastasis. Unraveling the molecular basis of lymphangiogenesis has been hampered by the lack of a small animal model that can be genetically manipulated. Here, we show that Xenopus tadpoles develop lymph vessels from lymphangioblasts or, through transdifferentiation, from venous endothelial cells. Lymphangiography showed that these lymph vessels drain lymph, through the lymph heart, to the venous circulation. Morpholino-mediated knockdown of the lymphangiogenic factor Prox1 caused lymph vessel defects and lymphedema by impairing lymphatic commitment. Knockdown of vascular endothelial growth factor C (VEGF-C) also induced lymph vessel defects and lymphedema, but primarily by affecting migration of lymphatic endothelial cells. Knockdown of VEGF-C also resulted in aberrant blood vessel formation in tadpoles. This tadpole model offers opportunities for the discovery of new regulators of lymphangiogenesis.
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated.
|
